The Role of Inflammatory Mediators in Altering Levels of Substance P During Post-Operative Tissue damage following surgery triggers the synthesis or release of endogenous, pro-inflammatory compounds. Inflammatory mediators may then initiate or maintain the process of inflammation and eventual wound healing. Substance P (SP), a neuropeptide released from primary afferent neurons, is involved in neurogenic inflammation, sensitization, and nociception/pain. However, relatively little is known about the interaction of inflarnmatory mediators or their effects on possibly altering the release of SP within acutely inflamed tissues. The validation and use of microdialysis probes are central to the objectives of this thesis research. The probe membrane facilitates the collection of inflammatory mediators directly from the surgical wound. Both clinical (third molar extraction model) and animal (rat incisor extraction model) paradigms will be tested in this series of studies. The inflammatory mediators bradykinin (iBK), prostaglandin E2 (iPGE2), prostacyclin (iPGI2), and leukotriene B4 (iLTB4), compounds with pro-inflammatory effects, will be collected and tissue levels quantified in the post-operative period. Also wound levels of iSP will be quantified as a marker of neurogenic inflammation. Studies involving healthy oral surgery patients will have the specific aims of: 1) validating the use of microdialysis probes for collecting tissue-derived iBK, iPGE2, iPGI2, LTB4, and iSP; 2) determining which mediators are involved in the anti-inflammatory effects of non-steroidals (NSAIDs) and corticosteroids (methylprednisol one), two families of drugs commonly used in the peri-operative period. The animal surgery model will allow studies evaluating the role of inflammatory mediators' receptors in altering tissue SP levels by administering selective receptor agonists and antagonists into the surgical wound. Together, the clinical and animal models will increase understanding of inflammatory processes and determine potentially new anti-inflammatory therapies of clinical relevance. Keywords: Post-Operative Pain, Inflammation, Microdialysis, Third Molar Surgery, Clinical Trial